Determination of glycated hemoglobin with special emphasis on biosensing methods

The glycated hemoglobin (HbA1c) level in blood is a measure of long-term glycemic status in patients with diabetes mellitus. Current clinical methods for determination of the HbA1c level include electrophoresis/electroendosmosis, ion exchange chromatography, high-performance liquid chromatography, boronate affinity chromatography, immunoassay, and liquid chromatography-tandem mass spectroscopy in addition to fluorometry and colorimetry. These methods have certain drawbacks such as being complex, time-consuming, and requiring expensive apparatus and trained persons to operate. These drawbacks were overcome by biosensing methods. We review these biosensors, which are based on (i) measurement of electrons, that is, current generated from splitting of hydrogen peroxide released during oxidation of fructosyl valine by immobilized fructosyl amino acid oxidase, which is directly proportional to HbA1c concentration, and (ii) direct measurement of HbA1c by some specific reaction. HbA1c biosensors work optimally within 4 to 1800 s, between pH 7.0 and 9.0 and between 25 and 45 °C, and in the range of 1 to 10,000 μM, with a detection limit between 20 and 500 μM and sensitivity between 4.6 nA and 21.5 μA mM⁻¹ cm⁻² and stable over a period of 5 to 90 days. We suggest the ways to modify existing HbA1c biosensors, leading to simple, reliable, and economical sensors ideally suited for point-of-care treatment.